6CE0
Crystal structure of a HIV-1 clade B tier-3 isolate H078.14 UFO-BG Env trimer in complex with broadly neutralizing Fabs PGT124 and 35O22 at 4.6 Angstrom
Summary for 6CE0
| Entry DOI | 10.2210/pdb6ce0/pdb |
| Descriptor | Envelope glycoprotein gp160, alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-3)-alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (12 entities in total) |
| Functional Keywords | hiv-1 gp140, uncleaved prefusion-optimized (ufo), immune system, viral-protein complex, viral envelope trimer, broadly neutralizing antibody, viral protein, viral protein-immune system complex, viral protein/immune system |
| Biological source | Human immunodeficiency virus 1 More |
| Total number of polymer chains | 6 |
| Total formula weight | 176937.82 |
| Authors | Kumar, S.,Sarkar, A.,Wilson, I.A. (deposition date: 2018-02-09, release date: 2018-12-05, Last modification date: 2023-10-04) |
| Primary citation | He, L.,Kumar, S.,Allen, J.D.,Huang, D.,Lin, X.,Mann, C.J.,Saye-Francisco, K.L.,Copps, J.,Sarkar, A.,Blizard, G.S.,Ozorowski, G.,Sok, D.,Crispin, M.,Ward, A.B.,Nemazee, D.,Burton, D.R.,Wilson, I.A.,Zhu, J. HIV-1 vaccine design through minimizing envelope metastability. Sci Adv, 4:eaau6769-eaau6769, 2018 Cited by PubMed Abstract: Overcoming envelope metastability is crucial to trimer-based HIV-1 vaccine design. Here, we present a coherent vaccine strategy by minimizing metastability. For 10 strains across five clades, we demonstrate that the gp41 ectodomain (gp41) is the main source of envelope metastability by replacing wild-type gp41 with BG505 gp41 of the uncleaved prefusion-optimized (UFO) design. These gp41-swapped trimers can be produced in CHO cells with high yield and high purity. The crystal structure of a gp41-swapped trimer elucidates how a neutralization-resistant tier 3 virus evades antibody recognition of the V2 apex. UFO trimers of transmitted/founder viruses and UFO trimers containing a consensus-based ancestral gp41 suggest an evolutionary root of metastability. The gp41-stabilized trimers can be readily displayed on 24- and 60-meric nanoparticles, with incorporation of additional T cell help illustrated for a hyperstable 60-mer, I3-01. In mice and rabbits, these gp140 nanoparticles induced tier 2 neutralizing antibody responses more effectively than soluble trimers. PubMed: 30474059DOI: 10.1126/sciadv.aau6769 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (4.602 Å) |
Structure validation
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